Comparison of Gut Microbiota in Two Different Maternal Exposure Models of Autism Spectrum Disorder in Mice.

IF 1.3 Q3 PSYCHIATRY
Alpha psychiatry Pub Date : 2025-02-28 eCollection Date: 2025-02-01 DOI:10.31083/AP38790
Qiang Zhang, Xuying Pang, Min Guo, Yuezhu Wang, Yu Xu, Quan Li, Huajun Zheng
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Abstract

Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with unknown etiology and unclear pathogenesis. Although construction of animal models of ASD using chemical exposure during pregnancy is a mature technique, the gut microbiota of these exposure models induced using different chemicals in mice have not been compared.

Methods: To compare the effects of exposure to different chemicals during pregnancy on the composition of gut microbiota in offspring, we treated Institute of Cancer Research (ICR) mice with lipopolysaccharide (LPS) and valproic acid (VPA) during pregnancy to construct different offspring ASD mouse models. After successful model construction, the gut microbiota of these models were studied.

Results: After adjusting for the random effects of the litter, the two groups showed a significant reduction in social time (social deficits) and an increase in self-grooming behaviors (repetitive and stereotyped behaviors). Gut microbiota analysis revealed significant changes, mostly a decrease, in the abundance of four phyla, 52 genera, and 41 species in the two types of ASD models. Several different gut microbes could be related to the development of ASD.

Conclusions: Chemicals exposure during pregnancy induces ASD-related behavioral abnormalities in offspring mice. Importantly, exposure to different chemicals during pregnancy produces varying degrees of effects on gut microbiota composition in offspring ASD models. This finding can provide a reference for studies on the etiology and pathogenesis of ASD.

两种不同母体暴露模式小鼠自闭症谱系障碍的肠道菌群比较
背景:自闭症谱系障碍(Autism spectrum disorder, ASD)是一组病因不明、发病机制不明确的神经发育障碍。虽然在怀孕期间使用化学物质暴露构建ASD动物模型是一种成熟的技术,但使用不同化学物质诱导的这些暴露模型的小鼠肠道微生物群尚未进行比较。方法:为了比较怀孕期间暴露于不同化学物质对子代肠道微生物群组成的影响,我们在怀孕期间用脂多糖(LPS)和丙戊酸(VPA)治疗癌症研究所(ICR)小鼠,建立不同的后代ASD小鼠模型。模型构建成功后,对这些模型的肠道微生物群进行了研究。结果:在调整了狗窝的随机效应后,两组狗的社交时间(社交缺陷)显著减少,自我梳理行为(重复和刻板行为)显著增加。肠道菌群分析显示,两种ASD模型中4门52属41种的丰度发生了显著变化,以减少为主。几种不同的肠道微生物可能与自闭症谱系障碍的发展有关。结论:妊娠期化学物质暴露可诱导子代小鼠出现与自闭症相关的行为异常。重要的是,怀孕期间接触不同的化学物质会对后代ASD模型中的肠道微生物群组成产生不同程度的影响。这一发现可为进一步研究ASD的病因及发病机制提供参考。
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